My broad long-term research objective is to develop an effective nanomedicine platform for targeted delivery of the photosensitizer drug Pc 4 to sites of head and neck cancer to enhance the clinical repertoire of Pc 4- induced photodynamic therapy (PDT) in these malignancies. Cancers of the buccal cavity, head and neck subset, larynx, pharynx, and nose/nasal passages is the seventh most common cause of cancer death in the US. In these cancers, the locoregional occurrence of new primary tumors after conventional radiotherapy and chemotherapy makes repetition of these therapies or surgery non-feasible, due to limitations of physical and emotional trauma, functional debilitation and aesthetic damage. In such cases, PDT may enable treating these cancers effectively while preserving tissue functionality and aesthetics. PDT involves administration and photoactivation of a photosensitizer (PS) drug, which leads to generation of singlet atomic oxygen that induces cell death. Due to simplicity, minimal damage and cost-effectiveness, this approach is currently being investigated for treatment of a variety of cancers, with promising results. My proposed research rationale is that, since overexpression of Epidermal Growth Factor Receptors (EGFR) is implicated in the aggressiveness of these malignancies, EGFR-targeted biocompatible micelles encapsulating Pc 4 can enhance the selective delivery and uptake of Pc 4 at sites of head &neck (including oropharyngeal) cancers, thereby enabling site- selective Pc 4-PDT. The specific aims are to: (1) Determine encapsulation and release kinetics of Pc 4 in biocompatible block-copolymer micelles, (2) Modify micelle surface with EGFR-specific ligands or antibodies and investigate cancer cell targeting of the surface-modified micelles in vitro, and, (3) Investigate targeted PDT effects on SCC cell lines in vitro and suitable animal models in vivo with Pc 4- loaded EGFR-targeted micelle formulations. The research is relevant to the mission of National Institute of Dental and Craniofacial Research (NIDCR), since it involves basic and applicative research in the biomedical area that will help me enhance my research expertise and experience for further progressing my career into healthcare research in the area of cancer therapy. My proposed research of developing novel therapeutic strategies for oropharyngeal malignancies appropriately complies with the vision of NIDCR for advancing oral health of all people and supporting scientific investigations for promoting well-being of the Nation. PUBLIC HEALTH RELEVANCE: The research will potentially generate insight in the form of manuscripts and invention disclosures that will facilitate timely transfer of knowledge for the betterment of public health. Since this class of cancers form 6% of all malignancies in the US and the seventh most common cause of cancer death, especially in people over 50, the proposed therapeutic system, if successful, can have significant benefit to public health.